Global profile of individuals undergoing total knee replacement through the PROGRESS-PLUS equity lens: Protocol for a systematic review.

Background: Osteoarthritis (OA) is a heterogenous degenerative disorder often causing destructive joint changes with severe pain and functional disability. Modifiable and non-modifiable risk factors, social context and psychological factors influence the development and progression of the disease. Total knee replacement (TKR) aims at reducing pain and improving function and is more successful with pre-operative and post-operative rehabilitation. However, most international research on rehabilitation interventions is conducted in high income contexts. Objective: The aim of our systematic review is to gain an overview of the demographic and social profiles of adults undergoing TKR for primary knee OA in lower, middle- and high-income countries through a health equity lens to inform the translation of intervention research in local contexts. Methods: A systematic review will be conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Eligibility criteria include observational studies and grey literature (theses) since the beginning of the databases reporting on demographic data of adults awaiting or undergoing TKR surgery. The PROGRESS-Plus framework will be used to describe equity elements. Results: A narrative summary and description of the global profile of individuals undergoing total knee replacement for osteoarthritis. Conclusion: A snapshot of the global demographic and social profile of individuals receiving TKR for primary knee OA through an equity lens will shed light on the similarities and differences between individuals from different contexts. Global demographic profile information may inform or assist in the development of translational strategies for evidence-based rehabilitation. Clinical implications: Translation of existing rehabilitation interventions to local contexts could improve pre-operative and post-operative outcomes for individuals on our surgical waiting lists.

Sensitization of the UPR by loss of PPP1R15A promotes fibrosis and senescence in IPF.

The unfolded protein response (UPR) is a direct consequence of cellular endoplasmic reticulum (ER) stress and a key disease driving mechanism in IPF. The resolution of the UPR is directed by PPP1R15A (GADD34) and leads to the restoration of normal ribosomal activity. While the role of PPP1R15A has been explored in lung epithelial cells, the role of this UPR resolving factor has yet to be explored in lung mesenchymal cells. The objective of the current study was to determine the expression and role of PPP1R15A in IPF fibroblasts and in a bleomycin-induced lung fibrosis model. A survey of IPF lung tissue revealed that PPP1R15A expression was markedly reduced. Targeting PPP1R15A in primary fibroblasts modulated TGF-ß-induced fibroblast to myofibroblast differentiation and exacerbated pulmonary fibrosis in bleomycin-challenged mice. Interestingly, the loss of PPP1R15A appeared to promote lung fibroblast senescence. Taken together, our findings demonstrate the major role of PPP1R15A in the regulation of lung mesenchymal cells, and regulation of PPP1R15A may represent a novel therapeutic strategy in IPF.

Health system challenges affecting rehabilitation services in South Africa.

BACKGROUND: The World Health Organization (WHO) recommends that access to rehabilitation is a human right. To date, however, rehabilitation in South Africa has not been a health priority. The focus has rather been on saving lives from communicable diseases such as HIV/AIDs and TB, which has been increasingly successful. Whilst more South Africans are now living with pharmacologically managed chronic, communicable diseases, they often suffer significant challenges to their physical and mental health. Moreover, there are many health conditions in South Africa that have not attracted as much attention, and which also compromise individuals' capacity to contribute effectively to their own wellbeing, that of their families and communities, and to the general economy. These include birth trauma, degenerative neurological conditions, acquired injuries such as spinal cord damage, limb amputation or head trauma, and chronic noncommunicable diseases (heart or kidney disease, stroke). In the absence of robust prevalence studies, it is estimated that one-in-three adults suffer from at least one chronic health challenge. For South Africa not to invest in rehabilitation is counter-productive, as it means that a significant percentage of its population cannot contribute to its economy. In the face of scant health resources to underpin equitable rehabilitation services, evidence needs to be provided to demonstrate that for increased expenditure on rehabilitation, there will be increased return at individual, family, society, and country levels. PURPOSE: This article presents challenges and solutions to ensure that South Africa can meet WHO 2030 Rehabilitation Goals for equitable provision of effective public rehabilitation services using the WHO's health system building block framework.IMPLICATIONS FOR REHABILITATIONTo meet the challenge of providing rehabilitation for those in need requires country-specific, strategic, evidence-informed, and planned decisions in terms of best investment for highest return.Whilst there is sound international evidence for best-practice rehabilitation care, country-specific strategies are required to identify and address local barriers to evidence implementation.In South Africa, where rehabilitation has not been a priority to date, it is important that a planned and well-costed approach is taken to ensure provision of equitable, accessible, affordable, and evidence-based rehabilitation.Measuring social, economic, and educational return on investment from rehabilitation should be part of the South African service-delivery planning process.National data could be obtained through adding additional questions on disability to the national census and through local surveys and reports at various public health care facilities.

Demographic transformation of the physiotherapy profession in South Africa: A retrospective analysis of HPCSA registrations from 1938 to 2018.

RATIONALE, AIM AND OBJECTIVE: The physiotherapy profession did not escape the effects of racially based segregatory practises. While numerous strategies and initiatives have been employed to redress the inequities of the past, the extent of demographic transformation within the physiotherapy profession in South Africa remains uncertain. Transformation is defined in this article as an intentional change aimed at addressing inequalities and the ultimate goal is for population group and gender profiles of higher education graduates to be representative of the national epidemiological profile. This paper describes the demographic patterns of Health Professions Council of South Africa (HPCSA) registered physiotherapists from 1938 to 2018. METHOD: A retrospective record review of the HPCSA database from 1938 until 2018 was performed. De-identified data were extracted, coded and analyzed for descriptive purposes. Z-tests were used for analysis of proportion differences, along with P-values and 95% confidence intervals for interpretation. RESULTS: In 2018, 7663 physiotherapists (6350 women and 1313 men) were registered with the HPCSA. Most registered physiotherapists (55.6%) were classified as white, followed by black (17.3%), coloured (10.3%) and Indian (9.8%). A progressive increase was found in the number of new registrations over time (1949-2018) by black (0.00%-24.38% of total new registrations), coloured (0.00%-15.47%) and Indian individuals (0.00%-10.03%), with a statistically significant increase in newly registered black therapists in the decade prior to 2018 (P = .005). Gender transformation appears to be occurring at a slower pace as the profession remains female-dominated (82.9% of registered physiotherapists in 2018). CONCLUSION: There has been a steady transformation of the South African physiotherapy graduates composition regarding population categories and gender. However, it is clear that much more than selection criteria is needed to transform the profession in a way that is nationally representative, remain actively accountable for transformation and apt for local context.

An inhalation anaesthesia approach for neonatal mice allowing streamlined stereotactic injection in the brain.

BACKGROUND: Investigating brain function requires tools and techniques to visualise, modify and manipulate neuronal tissue. One powerful and popular method is intracerebral injection of customised viruses, allowing expression of exogenous transgenes. This technique is a standard procedure for adult mice, and is used by laboratories worldwide. Use of neonatal animals in scientific research allows investigation of developing tissues and enables long-term study of cell populations. However, procedures on neonatal mice are more challenging, due to the lack of reliable methods and apparatus for anaesthesia of these animals. NEW METHOD: Here, we report an inhalation-based protocol for anaesthesia of neonatal (P0-2) mice and present a custom 3D-printed apparatus for maintenance of anaesthesia during surgical procedures. Our optimised method of anaesthesia enables a rapid method of stereotactic injection in neonatal mice for transduction of brain tissue. RESULTS AND COMPARISON WITH EXISTING METHODS: This approach significantly enhances animal welfare and facilitates wider and simpler use of neonatal rodents in scientific research. We demonstrate this procedure for targeted labelling of specific brain regions, and in vivo modification of tissue prior to organotypic culture. CONCLUSIONS: Our protocol for reliable delivery of inhalational anaesthetics can be readily adopted by any laboratory and will enable safer use of neonatal rodents across a diverse spectrum of scientific disciplines. Application to stereotactic injections allows a rapid and efficient method for modification of brain tissue.

Rehabilitation needs in individuals with knee OA in rural Western Cape, South Africa: an exploratory qualitative study.

BACKGROUND: Current clinical practice guidelines have suggested that each individual with knee osteoarthritis (OA) should receive three core treatments from their health care provider. These core treatments comprise of exercise, education and weight loss. Identification of the health care and rehabilitation needs of individuals with knee OA in rural areas are imperative for focusing service delivery in a specific context in order to empower the individual. The aim of this study was to explore the rehabilitation needs of individuals with knee OA living in rural Western Cape in order to identify the gaps in services offered and inform rehabilitation programmes in these settings. METHODS: Semi-structured in-depth individual interviews were performed on 16 individuals with knee OA living in rural settings of the Western Cape, South Africa. A deductive data analysis approach was used and the needs of the individuals were identified and categorised for interpretation and comparison with the reported services received. FINDINGS: The three major themes identified were 'I would like to know more', 'There's not much support from the clinic' and 'I don't feel myself anymore'. These themes relate to the lack of disease-specific education, barriers in the health systems and service delivery resulting in individuals lack of self-worth and poor mental wellbeing. The results revealed the integral relationship between health care systems, service delivery and the effect on patient wellbeing. CONCLUSION: The rehabilitation needs of individuals with knee OA in rural areas advocates for addressing barriers in rural primary health care system such as adequate human resources, referral systems and continuity of care. This will allow for a comprehensive, person-centred and context-specific multidisciplinary approach focused on empowering individuals with knee OA through disease-specific education, improving functional participation and symptom management strategies. This could improve the social inclusion and mental wellbeing of individuals living with knee OA.

Spinal tuberculosis: A systematic review of case studies and development of an evidence-based clinical guidance tool for early detection.

RATIONALE, AIMS, AND OBJECTIVES: Despite research being done on spinal tuberculosis, diagnosing this condition at an early stage remains problematic due to its insidious onset and the varying symptoms being associated. Most individuals present to the health care facility with either simple back pain at an early stage or neurological complications at a later stage, when spinal compression and vertebral collapse have occurred as a result of delayed diagnosis. The prevention of secondary complications is therefore dependent on early recognition and diagnosis. The objective of this review was to identify common clinical patterns in case presentations and develop an evidence-based clinical guidance tool to assist clinicians in the early identification of spinal tuberculosis. METHOD: A comprehensive literature search was conducted for published spinal tuberculosis case studies, which yielded 28 cases after critical appraisal. Data from the studies were categorized in order to assist with a factor analysis and the development of an evidence framework for screening and diagnosing spinal tuberculosis. An evidence-based clinical guidance tool was then designed from the data obtained. RESULTS: Factors associated with spinal tuberculosis and frequently reported symptoms and physical signs with which the patient could present upon assessment were identified. Options for investigations at primary, secondary, and tertiary levels were also identified. CONCLUSION: Through the use of an evidence-based clinical guidance tool, the clinician could be guided in the early suspicion and management of individuals with spinal tuberculosis and prevention of secondary complications.

Bacterial resistance to Quaternary Ammonium Compounds (QAC) disinfectants.

Control of bacterial diseases has, for many years, been dependent on the use of antibiotics. Due to the high levels of efficacy of antibiotics in the past other disease control options have, to a large extent, been neglected. Mankind is now facing an increasing problem with antibiotic resistance. In an effort to retain some antibiotics for human use, there are moves afoot to limit or even ban the use of antibiotics in animal production. The use of antibiotics as growth promoters have been banned in the European Union and the USA. The potential ban on the use of antibiotics to treat diseases in production animals creates a dilemma for man-suffer significant problem with bacterial infection or suffer from a severe shortage of food! There are other options for the control of bacterial diseases. These include vaccine development, bacteriophage therapy, and improved biosecurity. Vaccine development against bacterial pathogens, particularly opportunistic pathogens, is often very challenging, as in many cases the molecular basis of the virulence is not always clearly understood. This is particularly true for Escherichia coli. Biosecurity (disinfection) has been a highly neglected area in disease control. With the ever-increasing problems with antibiotic resistance-the focus should return to improvements in biosecurity. As with antibiotics, bacteria also have mechanisms for resistance to disinfectants. To ensure that we do not replace one set of problems (increasing antibiotic resistance) with another (increasing resistance to disinfectants) we need to fully understand the modes of action of disinfectants and how the bacteria develop resistance to these disinfectants. Molecular studies have been undertaken to relate the presence of QAC resistance genes in bacteria to their levels of sensitivity to different generations of QAC-based products. The mode of action of QAC on bacteria has been studied using NanoSAM technology, where it was revealed that the QAC causes disruption of the bacterial cell wall and leaking of the cytoplasm out of the cells. Our main focus is on the control of bacterial and viral diseases in the poultry industry in a post-antibiotic era, but the principles remain similar for disease control in any veterinary field as well as in human medicine.